PB1941: PRELIMINARY EXPLORATION OF PROLONGED USE OF ELTROMBOPAG IN PATIENTS WITH NAÏVE SEVERE APLASTIC ANEMIA IN THE REAL WORLD: DURATION AND EFFICACY
Authors: R. Li, Z. Liu, X. Chen, Q. Long, Y. Yang, S. Lin, J. Jia, G. He, J. Li
Journal: HemaSphere (2022)

Background: Eltrombopag (E-PAG) plus the immunosuppressive therapy (IST) consisted by antithymocyte immunoglobulin (ATG) and cyclosporin (CsA) has been reported with better efficacy in both refractory and naïve severe aplastic anemia (SAA) patients than IST alone. E-PAG was used up to 6 months in clinical trials. Patients with refractory SAA who remained on E-PAG with a median duration of 12 months showed further hematological improvement. Aims: To explore whether patients with naïve SAA could benefit from continuous use of E-PAG beyond 6 months and when E-PAG should be withdrawn in patients with no response. Methods: From February 2018 to November 2021, we collected 57 Chinese adult patients with naïve SAA who were treated with rabbit-ATG based IST (r-ATG, 3.5mg/kg/d × 5d and CsA 3-5 mg/kg/d) combining with E-PAG at dose of 75mg per day in the China Eastern Cooperation Group for Anemia (Clinical trials: ChiCTR2100045895). All patients were treated with E-PAG at least 6 months, and then whether to continue treatment was decided by the attending doctor according to patients’ situation. The dosage of E-PAG would be tapered gradually at 3 months after complete remission (CR) or 6 months after stable partial remission (PR). Results: Clinical and laboratory characteristics of patients were listed in Table 1. The median time from diagnosis to treatment was 3 weeks (1 week to 291 weeks). The median follow-up time was 17 months (1 month to 44 months) and overall survival rate was 98%. The overall response rates were 35% (20 of 57), 67% (36 of 54), 84% (42 of 50) and 95% (41 of 43) at 1, 3, 6 and 12 months, and CR rates were 17% (9 of 54), 24% (12 of 50) and 35% (15 of 43) at 3, 6 and 12 months. The first response was observed at 2 weeks after treatment, and the median time to remission during the first 6 months was 11 weeks (2 weeks to 25 weeks). 11% of patients achieved efficacy between 7 and 12 months. In patients with NR after continuous use of E-PAG for 12 months, no more patients met criteria for PR by extending the treatment of E-PAG. The cumulative effect curve showed that 88 percent of all 12 months responses occurred within 6 months, and the efficacy reached a peak at 6 months (Figure 1). 11 patients (22%, 11 of 50) who achieved CR within 6 months were under steady state with the exception of 1 patient converting to paroxysmal nocturnal hemoglobinuria at 12 months after treatment. In 30 patients achieved PR at 6 months, 5 patients (17%, 5 of 30) discontinued E-PAG after 6 months and 25 patients had a continuous exposure to E-PAG, while the efficacy of 13 patients (52%, 13 of 25) were improved to CR within median extended usage time of 9 months (2 to 31 months) of E-PAG, and the dose of E-PAG was tapered gradually in 6 patients (24%, 6 of 25), maintained at 75mg per day in 7 patients (28%, 7 of 25). The other 12 patients (48%, 12 of 25) were in stable PR. In 8 patients (16%, 8 of 50) were ineffective at 6 months, 1 patient died early at 1 month; 2 patients achieved PR at 12 months by E-PAG continuously; 5 patients treated with CsA alone latter; and 2 patients achieved CR at 12 months, 3 patients still were in NR in CsA alone group. Image:Summary/Conclusion: It was suggested that E-PAG was used at least 6 months. Continuous administration of E-PAG could improve the hematological response of PR patients to CR. No patient with NR taking effect after 12 months, new options should be considered with caution for them.